METABOLIC RESPONSES TO INTERLEUKIN-1 - CENTRALLY AND PERIPHERALLY MEDIATED

Objective The purpose of this study was to differentiate between the c atabolic effects of interleukin-1 (IL-1) when infused into the central nervous system or into the periphery. Summary Background Data After i njury and infection, IL-1 has been found in the central nervous system . Chronic intracerebrovascular infusion of IL-1 produces protein catab olism, anorexia, and fever. However, IL-1 may act directly on liver an d bone marrow to elicit metabolic responses. Although IL-1 is thought to be involved in a number of metabolic responses associated with inju ry-inflammation, the sites of action are unclear. Methods Rats were im planted with chronic infusion pumps and received diluent or three dose s of IL-1 infused subcutaneously for 6 days, and a variety of response variables were measured. In a second study, doses were adjusted so th at similar systemic catabolic responses were obtained from peripheral and intracerebroventricular infusion of IL-1. The acute-phase response s then were compared in the two groups of animals receiving IL-1 by di fferent routes. Result Subcutaneously infused IL-1 elicited catabolic responses in a dose-response manner. Similar catabolic responses were achieved by infusing one tenth of the dose of IL-1 given subcutaneousl y into the central nervous system. Although similar systemic responses (protein catabolism, anorexia, fever, and weight loss) were observed with both routes of infusion, the subcutaneous infusion produced a muc h greater lymphocytosis, elevation in acute-phase reactants, and fall in serum iron and albumin. Conclusions The IL-1 appears to have differ ent effects depending on the site of production and site of action. Re gionalization of signal proteins such as IL-1 should be taken into con sideration when devising specific anticytokine treatment strategies.